“Over the past two decades, a large number of epidemiologic studies have shown an association between HIV and risk of atherosclerotic cardiovascular events such as myocardial infarction,” he says. “The magnitude of that risk appears to be about 1.5-2 fold higher risk in HIV vs. uninfected persons. However, these studies have almost exclusively been performed in the U.S., Europe or Canada. Whether the magnitude of this increased risk in HIV is the same in sub-Saharan Africa– where HIV prevalence rates are highest– is unclear.”

To try to find answers, Dr. Longenecker and his team recruited patients from both Cleveland and Kampala, Uganda -- both HIV-positive and HIV-negative. All the Ugandan patients were older than 45 and had at least one risk factor for cardiovascular disease, such as hypertension, diabetes, high cholesterol, smoking or family history. The Cleveland patients were all over age 40.

“With the Ugandans, we were trying to recruit a population that was really high-risk,” Dr. Longenecker says. “We specifically indicated in our inclusion criteria required that they have at least one risk factor for heart disease such as hypertension or diabetes. Many had both.”

All patients in the study underwent cardiac CT scans for coronary artery calcium scoring – a measure that hadn’t been done in previous studies of patients with HIV in sub-Saharan Africa.

“To our knowledge, no prior studies of this population have used cardiac CT to evaluate subclinical coronary atherosclerosis,” Dr. Longenecker says.

Dr. Longenecker and his team also measured participants’ biomarkers of inflammation and immune activation.

Study results, presented recently at the International AIDS Society meeting in Amsterdam, are striking. Dr. Longenecker and his team found that when they compared coronary calcium scores of Ugandans and Clevelanders living with HIV, the Ugandans’ scores were substantially lower, despite the fact that they had more cardiovascular risk factors. After controlling for age and other risk factors, Ugandans had 13 times lower odds of having a coronary artery calcium score over zero.

At the same time, the team found that Ugandans who did have subclinical coronary disease tended to have elevated biomarkers of inflammation and immune activation.

“This seems to be more strongly associated with subclinical coronary disease in the Ugandan population than in the U.S. population, even though the overall rates of subclinical coronary disease were lower,” Dr. Longenecker says. “It’s interesting when we think about what might be the drivers of inflammation and immune activation in Uganda. They are certainly different than what we see in the United States. In the U.S., they may have to do a lot with HIV-specific factors, such as how long they’ve had HIV, how bad was their HIV when they were first diagnosed and started on medicines, but also things like diet, environmental exposures, even social determinants of health. In Uganda, there may be different factors, such as exposure to particulate-matter pollution and exposure to parasites and helminth infections, those sorts of things.”

One area of inquiry Dr. Longenecker and his team are pursuing is whether latent tuberculosis (TB) infection may be one of those novel drivers of inflammation in a sub-Saharan African context. It’s estimated that about half of the people living in Uganda have latent TB.

“It has been proposed that having that low level exposure to TB, even if you don’t have active TB disease, may cause an immune response that leads to inflammation,” Dr. Longenecker says. “We’re asking these people to come back, two years after their initial exam with us, to do another cardiac CT scan and to have a TB test. We’ll look at whether those with latent TB have higher rates of subclinical coronary disease and whether they might have high-risk plaque features on CT coronary angiography, which would predispose them to coronary events like myocardial infarction.”

“There are other aspects to the study as well,” he says. “We are doing fresh whole blood flow cytometry on monocytes and other biomarkers. We’ve been able to take advantage of the sophisticated immunology resources that University Hospitals Cleveland Medical Center and Case Western Reserve University have helped to establish at the Joint Clinical Research Center in Uganda. This is very sophisticated immunology research that is able to be conducted there because of the investment that we have made over the past 25 years. It’s pretty exciting. In the end, we’ll be able to examine immune pathways that link inflammation with coronary disease in Uganda, even though the rates of coronary disease overall are lower than we might expect in the U.S. population. More generally, we’ll help build the knowledge base on cardiovascular disease among people living with HIV, especially in sub-Saharan Africa.”

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